People with major depressive disorder (MDD) have low concentrations of the molecule acetyl-L-carnitine (LAC) in their blood. Severe LAC deficiency is also associated with lower responses to anti-depressant medication. The finding could pave the way for a blood test not only for the presence of depression, but for its severity too, a potentially transformative step in the fight against mental illness. The same research also indicated that childhood trauma can lower LAC levels decades later, shedding light on its relationship with adult depression.

Rats with low levels of LAC have been found to show symptoms consistent with depression. LAC changes the expression of several genes important to healthy brain function, including preventing the loss of brain cells in the hippocampus. It also helps transport fatty acids into mitochondria so deficiencies could lead to many serious implications.

Dr Carla Nasca of Rockefeller University found something similar in humans, where the diagnosis of depression is probably more accurate since patients can confirm their symptoms. In the Proceedings of the National Academy of Sciences, Nasca and colleagues report that 71 acutely depressed patients averaged 25 percent lower LAC levels than 45 non-depressed counterparts of similar age.

Moreover, Nasca found low LAC levels correlated with more severe symptoms among the most depressed segments of her sample. The relationship was particularly strong for those who hadn't responded to anti-depressant medication, known as treatment-resistant depression (TRD). Histories of childhood sexual or physical abuse were associated with low LAC levels, as was emotional neglect in women with TRD, but not in men.

LAC supplementation in rats has been found to change their behavior and lead to brain changes that indicate their depression has improved. As a bonus, supplemented rats also experienced reduced insulin resistance. Nasca's work did not test the potential of such supplementation in humans.